PRPF8 Mutation-Induced Defects in Human iPSC-Derived RPE Are Rescued by Adenine Base Editing.

ABSTRACT:

Purpose

The pathological effects of pre-mRNA processing factor 8 (PRPF8) mutations on the retinal pigment epithelium (RPE) are not fully understood. We aimed to identify disease-specific cellular and molecular phenotypes in PRPF8 retinitis pigmentosa (RP) patient-derived induced pluripotent stem cell (iPSC)-RPE and to test whether adenine base editing (ABE), which corrects the PRPF8 mutation in iPSCs, can reverse abnormal RPE phenotypes.

Methods

We obtained patient-derived iPSCs with the heterozygous PRPF8 (c.5792C>T) mutation and created an induced mutation iPSC line by introducing the same mutation into wild-type iPSCs using CRISPR/Cas9. These cells were differentiated into RPE cells. We measured PRPF8 expression, barrier integrity, and apicobasal polarity. Electron micros

SUBMITTER: Sun X 

PROVIDER: S-EPMC12805961 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature